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Bleeding tendency, a prominent feature of patients with Gaucher disease (GD), is associated with abnormal platelet function. Brain-derived neurotrophic factor (BDNF) is a protein with neuroprotective potential stored in alpha granules of circulating platelets. Here we studied BDNF levels in 50 patients with type I GD (GD1) and their correlation with platelet activity and bleeding tendency. Flow cytometry was used to test unstimulated and stimulated measurement of platelet surface-activated expression of αIIbβ3 integrin, P-selectin and lysosomal-associated membrane protein (LAMP3/CD63). Serum and plasma BDNF levels were quantified using ELISA. The bleeding history was recorded by a bleeding questionnaire. Serum BDNF levels were positively correlated with platelet count and moderately correlated with unstimulated and stimulated platelet P-selectin expression. Patients with more than one bleeding manifestation were shown to have lower serum BDNF levels, albeit similar platelet count. Plasma BDNF levels were significantly elevated in splenectomized patients and showed a moderate positive correlation with stimulated platelet CD63 expression. These observations demonstrate the first association between BDNF levels in the peripheral blood with platelet dysfunction and increased bleeding manifestation. The role of measuring serum BDNF for assessing platelet alpha degranulation defects and bleeding risk in patients with GD and the general population needs further study.

Background: Bleeding disorders (BD) are under-recognized in adolescents with heavy menstrual bleeding (HMB)., Objectives: The lack of clinical guidelines and variable symptomatic management of HMB created the imperative to standardize HMB care to identify and manage BD in adolescents., Methods: We convened an international working group (WG), utilized the results of a literature review to define knowledge gaps in HMB care, and used the collective clinical experience of the WG to develop care considerations for adolescents with BD and HMB. We then solicited input on the appropriateness of HMB care considerations from expert stakeholders representing hematology, adolescent medicine, and obstetrics-gynecology. We conducted an expert panel online, using the ExpertLens platform. During a three-round online modified-Delphi process, the expert panel rated the appropriateness of 21 care considerations using a 9-point scale to designate care as appropriate (7-9), uncertain (4-6), or inappropriate (1-3) covering screening for BD, the laboratory work-up, and management of adolescents with BD that present with HMB. We used the RAND/UCLA appropriateness method to determine the existence of consensus among the interdisciplinary panel of experts., Results: Thirty-nine experts participated in the panel. The experts rated fifteen HMB care considerations as appropriate, six as uncertain, and none as inappropriate., Conclusions: The HMB care statements represent the first set of HMB care considerations in adolescents with BD, developed with broad expert input on appropriateness. Although likely to be of interest to a range of clinicians who routinely manage adolescents with HMB, additional research is required in many key areas., (© 2020 International Society on Thrombosis and Haemostasis.)

The maturation and postnatal development of the human coagulation system was first studied and described more than 20 years ago. These older studies, supported by more recent data, confirm the significant and important differences in the physiology of coagulation and fibrinolysis in neonates and young children compared with older children and adults. Subsequently, significant differences were also described in the physiology of primary hemostasis and in global in vitro tests for hemostasis. These differences, which mostly reflect the immaturity of the neonatal hemostasis system, are functionally balanced. Healthy neonates show no signs of easy bruising or other bleeding diathesis and no increased tendency to thrombosis for any given stimulus compared with adults. Systemic diseases may affect hemostasis, predisposing ill neonates to increased hemorrhagic or thrombotic complications. The immaturity of the hemostasis system in preterm and very-low-birth-weight neonates may contribute to a higher risk for intraventricular hemorrhage. Therapies targeting the hemostasis system can be effective for preventing and treating these events. The concept of "neonatal coagulopathy" has an important impact on both the diagnosis and management of hemorrhagic or thrombotic events in neonates. For diagnosis of hemostasis disorders, diagnostic laboratories processing pediatric samples should use age-, analyzer-, and reagent-appropriate reference ranges. Age-specific guidelines should be followed for the management of neonates with hemostatic disorders.

Children presenting with bleeding symptoms pose a diagnostic challenge. The evaluation should include a comprehensive medical and bleeding history, detailed family history, a physical examination, and selected laboratory tests. Evaluation of the bleeding history should include an objective quantitation of the bleeding symptoms, followed by objective quantitation of the family members' bleeding symptoms. If a bleeding disorder is suspected, based on personal and/or family bleeding history, specific laboratory testing is needed for attaining a diagnosis. The screening tests for coagulation factor deficiencies are considered reliable, routinely available, and easy to perform. However, for primary hemostatic defects, the various screening tests have not yet proven to be reliable and thus referral for a specialized hematology consultation and specific laboratory testing are needed. Perhaps a Bayes theorem approach, combining the personal and family bleeding history with the results of a screening test for a primary hemostatic defect would prove to be useful in the identification of those children who will most benefit from specific laboratory testing., (© Thieme Medical Publishers.)

A cross-sectional retrospective study was performed to question the utility of coagulation screening to prevent procedure-related bleeding before oocyte retrieval in IVF. Among 1,032 patients evaluated we found that 534 coagulation tests were needed to prevent one case of bleeding associated with an abnormal coagulation test result., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: A convenient screening test for children with bleeding symptoms before more labor-intensive diagnostic steps are taken would be of value. The Impact-R was designed in an attempt to analyse platelet function under near physiological conditions. Results are presented as surface coverage (SC, %) and average size (AS, microm(2))., Objective: In this cross-sectional retrospective study, we assessed the use of the Impact-R in the evaluation of children with a suspected bleeding disorder (BD)., Methods: The hospital charts of 110 children referred to the coagulation laboratory were reviewed for personal and family bleeding history (BH) as well as results of the laboratory evaluation., Results: A laboratory 'diagnosable' BD (LBD) was found in 23 children (21%, 95% CI 14-30%). A diagnosis of LBD was associated with the severity of bleeding but not with family BH. By receiver-operating characteristic (ROC) curve analysis, the SC was superior to the AS for diagnosis of a LBD. The Impact-R was abnormal in 43/97 children (44.3%, 95% CI 34-55%). The predictive values of a normal and abnormal Impact-R were 96% (95% CI 92-97%) and 42% (95% CI 28-56%), respectively. When considering the personal and family BH, the post-test probability for LBD after a normal Impact-R was reduced from 20% to 3.5% (95% CI 2.5-7%)., Conclusions: A normal Impact-R test is highly effective in excluding LBDs. Yet, in case of an abnormal Impact-R test, further testing is needed. An algorithm that includes the personal and family BH and the results of a screening test may improve the diagnostic process. Prospective studies are now needed to confirm these findings.